Changes in the ability of the body to handle drugs are known to occur with aging, and the elderly are less tolerant of drugs than younger individuals. Altered drug metabolism may play an important role in the increased susceptibility to drugs as well as disease due to environmental factors. Glutathione (GSH) and glutathione-S-transferase activity reflect a major pathway of drug metabolism that may be age related. We have recently shown that GSH levels in blood, kidneys and intestines as well as total (oxidized and reduced) glutathione in liver decrease with advanced age in mice. Furthermore, the activities also decrease with advanced age in hepatic and extrahepatic tissues. We shall correlate the above results with glutathione turnover rates in mice of various age, the ability of acetaminophen to deplete glutathione in selected tissues as a function of age, and the effect of penicillamine feeding on glutathione levels in selected tissues of mice. We shall extend the drug metabolism and blood cell studies. A direct correlation of blood tissue GSH with altered drug metabolism has the potential of utilizing blood GSH as a clinical index of metabolic aging.